The Pain Practitioner

docereclinics

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american academy of

pain management

Integrative No Life Limited Pain Management by Pain

for Optimal Patient Care

The Pain Practitioner

Winter 2015 2013

No Life Limited By Pain 2015

THE 26TH ANNUAL M EETING

INSIDE: 2015 Annual Meeting Review,

Blue Ribbon Poster Abstract Winners, Autologous Stem Cell Therapy, and more!


FROM THE CLINIC

Autologous Stem Cell Therapy

A NATUROPATHIC APPROACH FOR THE TREATMENT OF CHRONIC

MUSCULOSKELETAL PAIN CONDITIONS—Part ll of ll

HARRY ADELSON, ND

Part I of this series, published in the Fall 2015 issue of The

Pain Practitioner, provided an overview of the fundamental

methods employed by the naturopathic physician for laying a

foundation of optimal cellular metabolism, connective tissue

health, and overall function in order to optimize stem cell therapy.

Part II details the methods for harvest and concentration/

isolation of bone marrow aspirate concentrate (BMAC) and

adipose-derived stromal vascular fraction (SVF) and includes

original research comparing three arms treating low back pain

and osteoarthritis of the knee: 1) the use of bone marrow aspirate

concentrate (BMAC) alone; 2) the use of adipose-derived

stromal vascular fraction suspended in platelet rich plasma

(SVF/PRP); and 3) the use of adipose-derived stromal vascular

fraction suspended in BMAC (SVF/BMAC).

Summary

An emerging approach to the treatment of chronic musculoskeletal

pain is the use of autologous mesenchymal stem

cells (MSCs) harvested from a patient’s own bone marrow

or adipose tissue for reinjection into damaged or degenerated

joints, ligaments, tendons, and muscles. The purpose

of this retrospective survey was to compare patient-reported

outcomes after treatment of osteoarthritis of the knee or

low back pain in three treatment groups: patients injected

with bone marrow aspirate concentrate (BMAC), patients

injected with adipose-derived stromal vascular fraction

suspended in platelet rich plasma (SVF/PRP), and patients

injected with adipose-derived stromal vascular fraction suspended

in bone marrow aspirate concentrate (SVF/BMAC).

Based on patient reports, patients injected with BMAC had

consistently satisfactory results, patients injected with SVF/

PRP either had results superior to BMAC or no improvement

at all, and patients injected with SVF/BMAC had

consistently satisfactory results superior to BMAC alone.

There were no adverse outcomes in any patient surveyed (N

= 95). Based on these results, injection of SVF/BMAC for

osteoarthritis of the knee and low back pain appears to be

safe and produces consistently satisfactory results.

Introduction

Mesenchymal stem cells (MSCs) have been dubbed

“patient-specific drug stores for injured tissues” because

of their ability to secrete bioactive factors and signals at

variable concentrations in response to local microenvironmental

cues (1). MSCs are found throughout the body in

many tissue types, but they are particularly abundant and

easily harvested from the medullary cavity of flat bones

and from adipose tissue (2,3). MSCs can be easily concentrated

from bone marrow with simple centrifugation. With

slightly more effort, MSCs can be isolated from adipose

tissue through a multistep process of incubation/enzymatic

digestion with collagenase followed by centrifugation and

filtration. When injected into the site of damage or degeneration,

MSCs release a spectrum of antiinflammatory, immunomodulatory,

and trophic factors that trigger the regeneration

and healing of connective tissues through activation

of stem cells endogenous to the site.

As the pool of data continues to grow, the site-specific

injection of autologous stem cells has shown promise in musculoskeletal

pain conditions such as osteoarthritis (4), sports

or traumatic injury (5), low back and discogenic pain (6),

neck pain with or without cervicogenic headaches (7), and

osteonecrosis (8). Of note, concurrent bodies of data continue

to grow that appear to refute the validity of arthroscopic

surgery for knee pain (9-11) and cast doubt upon the validity

of steroid epidural injections for low back pain (12,13).

Currently in the United States there are a growing

number of pain clinics offering autologous stem cell therapy

to patients suffering with musculoskeletal pain conditions.

Based on rudimentary internet searches and my own familiarity

with the industry, the majority of clinics that offer

autologous stem cell therapy offer either BMAC or SVF/

PRP, while significantly fewer clinics offer both. According

to their websites, clinics offering BMAC often claim bone

marrow-derived stem cells to be superior because of the

greater body of data supporting their use. Clinics offering

SVF/PRP often claim adipose derived stem cells to be superior

because of the much larger total MSC count produced

40 | THE PAIN PRACTITIONER | WINTER 2015


FROM THE CLINIC

FIGURE 1

Bone marrow aspiration from the iliac crest.

compared to BMAC. I am not aware of any studies directly

comparing bone marrow-derived stem cells to adipose-derived

stem cells and have seen no data evaluating the combination

of the two (SVF/BMAC) in a single treatment.

The purpose of this retrospective survey was to compare

patient-reported outcomes after treatment of osteoarthritis

of the knee and low back pain in three treatment groups:

patients injected with BMAC, patients injected with SVF/

PRP, and patients injected with SVF/BMAC.

Methods

Patients presenting to Docere Clinics in Park City, Utah,

between July 15, 2014, and November 15, 2014, who were

deemed candidates for autologous stem cell therapy, were

asked to choose between being treated with BMAC or SVF/

PRP. The conversation can be summarized as follows: “I can

do a bone marrow aspiration and treat you with BMAC,

with which I have five years of experience and am aware

of data supporting its use, or I can do a lipoaspiration and

a blood draw and treat you with SVF suspended in PRP,

which has the potential to provide us with a far greater

yield of stem cells and, theoretically, a superior outcome.

However I have little experience with it and there are very

few data supporting its use.” Patients then self-selected into

the BMAC or the SVF/PRP group.

Patients treated with BMAC underwent a fluoroscopically

guided bone marrow aspiration of 40 to 120 mL from

a single puncture at the site of the iliac crest. The puncture

was made on the thickest part of the posterior superior iliac

spine. The needle was oriented to be parallel to the flat bone,

and was rotated 90 degrees

and advanced 0.5 cm after

every 10 mL of marrow

aspirated (Figure 1). The

marrow was then centrifuged

for 10 minutes at

1,000 g and the buffy coat

drawn into one or more

10 mL treatment syringes.

In patients treated

with SVF/PRP, 100 mL

of adipose tissue, 50 mL

per side, was aspirated

from the flank region and

FIGURE 2

Fluoroscopically guided, intraarticular

injection of the knee.

FIGURE 3

Ultrasound-guided injection

of MCL.

40 mL to 120 mL of venous blood was drawn. In order to

isolate SVF, the adipose tissue was incubated and enzymatically

digested with collagenase, then centrifuged and

filtered (the entire process took approximately 45 minutes).

The blood was centrifuged for 10 minutes at 1,000 g and

concentrated in a “pure,” or “acellular” manner (devoid of

RBCs or WBCs). SVF was suspended in one or more 10

mL syringes of PRP.

Patients treated for osteoarthritis of the knee received

a fluoroscopically guided, intra-articular injection into

the knee (Figure 2). Ultrasound guidance was added for

patients who reported pain on palpation to the medial collateral

and lateral collateral ligament or supra/infra-patellar

tendon (Figure 3).

Patients treated for low back pain received fluoroscopically

guided injections bilaterally at the following locations,

THE PAIN PRACTITIONER | VOLUME 25 NUMBER 4 | 41


FROM THE CLINIC

FIGURE 4

Lumbar transforaminal

epidurals with stem cells.

FIGURE 5

Injection of stem cells into intervertebral discs

2 mL of injectate per location: perifacet at L2/3-L5/S1 levels,

and iliolumbar ligament, proximal and distal insertions,

and the sacroiliac ligament, in three locations. Patients

reporting radiculopathy/paresthesia received additional

lumbar transforaminal epidural injections of 5 mL of stem

cells (Figure 4). Intradiscal injections of 1.5 mL stem cells

were given to patients who reported mid-line pain that

worsened when bending forward and whose MRIs showed

desiccation (Figures 5).

Patients who had experienced pain for a minimum of

one year prior to treatment were asked to rate their percentage

of improvement on a numerical scale and whether

they experienced any adverse effects from treatment.

During this period and during preliminary follow-up

with patients, I began to notice a trend that many SVF/

PRP patients reported higher satisfaction than those in the

BMAC group, but the remainder were experiencing no

improvement at all. Beginning November 16, 2014, I began

offering patients SVF prepared as described above but

suspended in BMAC rather than PRP, hypothesizing that

the combination could offer the consistency of BMAC with

the augmented outcomes of SVF.

On August 1, 2015, we reviewed the charts of all

patients with knee arthritis and low back pain who were

treated with SVF/BMAC between November 15, 2014,

and March 15, 2015, to identify those who had experienced

pain for a minimum of one year prior to treatment.

They were asked to rate their percentage of improvement

on a numerical scale and whether they experienced any

adverse effects from treatment.

Results

Results (Table) were consistent between the two BMAC

groups. The average improvement reported in the knee

osteoarthritis group (n = 21) was 75.7%. One patient

reported only 10% improvement; the remainder reported

50% or better improvement. In the low back pain group

(n = 9), the average improvement was 70.6%. Only one

patient reported no improvement at all, and everyone else

reported 50% or better improvement.

Results were also consistent between the two SVF/PRP

groups. The average improvement reported in the knee osteoarthritis

group (n = 26) was 61.7% and in the low back

pain group (n = 14) the average improvement reported was

61.1%. However, in each group, there was a relatively higher

percentage of patients who did not respond to treatment

(26.9% and 28.6%, respectively). Patients who did respond

to treatment improved, on average, more than those in the

BMAC groups. Among responders, 84.5% of patients with

knee osteoarthritis reported improvement and 85.5% of

those with low back pain reported improvement.

Results were consistent between the two SVF/BMAC

groups. In the SVF/BMAC:OA knees group (n = 14), one

patient reported no improvement at all but everyone else

reported 75% or better improvement resulting in an average

of 81.5% improvement. In the BMAC:OA low back

pain group (n = 11), one patient also reported no improvement

but everyone else reported 80% or better improvement

resulting in an average of 80.9% improvement.

None of the patients surveyed (N = 95) experienced

complications or adverse reactions other than mild postprocedure

soreness.

Discussion

Based on patient reports, patients injected with BMAC had

consistently satisfactory results, patients injected with SVF/

PRP either had results superior to BMAC or no improvement

at all, and patients injected with SVF/BMAC had con-

42 | THE PAIN PRACTITIONER | WINTER 2015


FROM THE CLINIC

TABLE

Treatment Results for Autologous Stem Cell Therapy Options

BMAC:

OA knee

BMAC:

LBP

SVF/PRP:

OA knee

SVF/PRP:

LBP

SVF/BMAC:

OA knee

Number of patients 21 9 26 14 14 11

SVF/BMAC:

LBP

Male/female ratio 13 to 8 6 to 3 16 to 10 8 to 6 9 to 5 7 to 4

Age range/avg 35-83/60 29-76/45.7 38-85/63.7 38-71/58.9 44-81/59.5 39-73/54.8

BMI range/ave 21.9-

54.8/26.9

Avg number of

treatments

Avg % satisfaction

(total)

Number of

nonresponders (%)

Avg % satisfaction

(responders)

21.3-31/23.9 19.9-39.1/27.0 23.2-35.4/27.2 21.6-29.3/25.6 20-32.2/25.4

1.1 1.3 1 1 1.1 1

75.70 70.60 61.70 61.10 81.50 80.90

0 1(11.1) 7(26.9) 4(28.6) 1(7.1) 1(9.1)

75.70 79.39 84.50 85.50 87.65 89.0

MAC =

Bone marrow aspirate

concentrate

SVF/PRP =

Adipose-derived

stromal vascular

fraction suspended in

platelet-rich plasma

SVF/BMAC =

Adipose-derived

stromal vascular

fraction suspended in

bone marrow aspirate

concentrate

sistently satisfactory results superior to BMAC alone. There

were no adverse outcomes in any patient surveyed (N = 95).

These results caused me to question what was responsible

for the high non-responder rate in the SVF/PRP

groups. It appears that for those who responded, SVF/PRP

rendered a superior outcome to BMAC in both the OA

knee and lower back pain groups; however, nearly 30%

of the SVF/PRP patients treated had no benefit at all. An

analysis of results from responders only in all the groups

confirmed that the SVF/BMAC recipients had consistently

satisfactory results superior to BMAC and SVF/PRP alone.

It is entirely possible that the MSCs did not survive

the isolation process in the non-responder groups, which

would account for the high percentage of nonresponders

in the SVF/PRP group. A major flaw in the study is that

flow cytometry was not performed to determine MSC total

cell count and cell viability. I have since obtained a flow

cytometer and I am measuring cell count and cell viability

in all patients treated with stem cell therapy. Future study

will compare total cell count and cell viability to patientreported

outcomes.

Based on these results, injection of SVF/BMAC for osteoarthritis

of the knee and low back pain appears to be safe

and produces consistently satisfactory results.

Clearly, this series of simple surveys does not claim to

provide any hard evidence; it is merely intended as an empirical

report of one clinician’s experience in this new and

rapidly growing field.

References

1. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive

therapeutics for regenerative medicine. Exp Mol Med. 2013; 45:e54. doi:10.1038/

emm.2013.94.

2. Hendrich C, Engelmaier F, Waertel G, Krebs R, Jäger M. Safety of autologous bone

marrow aspiration concentrate transplantation: initial experiences in 101 patients.

Orthop Rev (Pavia). 2009 Oct 10; 1(2):e32.

3. Michalek J, Moster R, Lukac L, et al. Autologous adipose tissue-derived stromal vascular

fraction cells application in patients with osteoarthritis. Cell Transplant. 2015 Jan 20.

4. Goldberg, VM. Stem cells in osteoarthritis. HSS J. 2012 Feb;8(1):59-61.

5. Quintero AJ, Wright VJ, Fu FH, Huard J. Stem cells for the treatment of skeletal muscle

injury. Clin Sports Med. 2009;28(1):1-11.

6. Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J. Intervertebral

disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation.

2011 Oct 15;92(7):822-828.

7. Adelson H. Bone marrow and adipose derived autologous stem cells for the treatment

of chronic musculoskeletal pain. Paper presented at Annual Meeting of the American

Academy of Pain Management; September 2014; Phoenix, Arizona.

8. Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee

osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med

Case Rep. 2011 Jul 7;5:296.

9. Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic surgery for degenerative

knee: systematic review and meta-analysis of benefits and harms. Br J Sports Med.

2015 Oct;49(19):1229-35.

10. Moseley JB1, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery

for osteoarthritis of the knee. N EnglJ Med. 2002;347(2):81-88.

11. Kirkley A, Birmingham TB, Litchfield RB, et al. A randomized trial of arthroscopic

surgery for osteoarthritis of the knee. N EnglJ Med. 2008;359(11):1097-1107.

12. Radcliff K, Kepler C, Hilibrand A, et al. Epidural steroid injections are associated with less

improvement in the treatment of lumbar spinal stenosis: a subgroup analysis of the Spine

Patients Outcomes Research Trial. Spine (Phila Pa 1976). 2013 Feb 15;38(4):279-91.

13. Pinto RZ, Maher CG, Ferreira ML, et al. Epidural corticosteroid injections in the

management of sciatica: a systematic review and meta-analysis. Ann Intern Med. 2012

Dec 18;157(12):865-77.

Harry Adelson, ND, opened Docere Clinics in Salt Lake City in 2002,

and from day one his practice has been 100% regenerative injection

therapies for the treatment of musculoskeletal pain conditions. In 2006 he

incorporated platelet rich plasma and ultrasoundguided

injection into his armamentarium; in 2010,

bone marrow aspirate concentrate and adiposederived

stem cells; and in 2013, fluoroscopic-guided

injection. Since February of 2010, Dr. Adelson has

performed more than 3,000 bone marrow and

adipose-derived adult stem cell procedures, placing

him in the company of those most experienced in

the world with use of autologous stem cells for the

treatment of musculoskeletal pain conditions.

THE PAIN PRACTITIONER | VOLUME 25 NUMBER 4 | 43

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